The purpose of this study is to evaluate the virological efficacy of maintenance therapy with atazanavir with ritonavir combined with lamivudine in treatment experienced HIV positive patients with full and stable virological suppression.

Proportion of patients with viral load < 50 copies/mL at week 48 at the intention-to-treat with switch = failure analysis

Secondary Outcome Measures:

Efficacy and the safety of atazanavir with ritonavir combined with lamivudine in treatment experienced HIV positive patients with full and stable virological suppression [ Time Frame: 48 and 96 weeks ] [ Designated as safety issue: No ]

Current treatment guidelines recommend three drug regimens with a "backbone" of 2 nucleos(t)ide reverse transcriptase inhibitors (N(t)RTIs) and a "third drug" to be chosen among non-nucleoside reverse transcriptase inhibitors (NNRTIs) and ritonavir-boosted protease inhibitors (PIr). Regimens containing less than three antiretroviral drugs are currently not recommended based on the high risk of virological failure and selection of drug resistance mutations (DRM) with previous experience of NRTI-only based approaches with the exception of boosted PIs monotherapy which is optional in patients with intolerance to NRTIs or requiring treatment simplification provided that they never experienced virological failures or admitted in exceptional circumstances.

Nevertheless, the investigation of possible new treatment paradigms remains attractive due to the high potency and low risk of selection of drug resistance mutations with PIr based therapies and the established long term toxicity of even newer and currently preferred N(t)RTIs, in particular the renal and bone toxicity of tenofovir and the debated potential association with increased cardiovascular risk of abacavir, which has been described in some cohort studies. Studies evaluating N(t)RTI-sparing treatment strategies are thus increasing in order to try to respond to the unmet medical needs of HIV-infected patients with metabolic complications and increasing risk of cardiovascular or renal diseases.

These studies will need to investigate the safety and efficacy of these alternative strategies, also evaluating their possible effects on renal function, bone mass density and risk of premature osteoporosis.

Atazanavir with ritonavir is a generally well tolerated lipid-friendly protease inhibitor with mild effects on lipid metabolism even when combined with low-dose ritonavir and is the only drug who achieved a non-significant difference in virological efficacy compared to efavirenz; like all other PIr-based regimens, failure of an atazanavir/ritonavir containing cART seems to protect against the development of drug resistance mutations to both the PI and the backbone. Lamivudine is a well tolerated NRTI which showed no significant toxicity in the short and long term and, together with its analog emtricitabine, is now a preferred option in most of the major international treatment guidelines; it has a good CNS penetration score and its only signature resistance mutation (M184V) deeply impairs the viral fitness and does not compromise the future treatment options.

The combination of these two drugs could therefore be an appealing possibility for treatment switch in stably virologically suppressed treatment-experienced patients with toxicity-related issues. The results of a previously planned 24 weeks interim analysis of a monocentric 48 weeks Italian pilot study evaluating this strategy in 40 patients has recently been presented at IAS conference in Vienna and showed no virologic failures without any "blip" and good tolerability with a significant improvement of renal function as measured by MDRD. These data look very promising and allow us to be confident in designing a randomized study in order to confirm these findings.

Eligibility

Ages Eligible for Study:

18 Years to 80 Years

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria

HIV positive patients 18 years of age or older who signed an informed consent form

Already on cART, without any treatment interruption.

Treated with a cART regimen containing atazanavir boosted with ritonavir since at least 3 months

With full virological suppression (VL<50 copies/mL) for a minimum of six months and in at least in two consecutive determination 3 months +/-2 weeks apart from each other

With CD4 cell count >200 since at least 6 months and without opportunistic infections or other AIDS-related events since at least one year before screening

Patients with non-AIDS related illnesses which could, in the Clinician's judgement, jeopardize the patient's compliance to the study procedures (i.e. Child-Pugh B or higher liver cirrhosis, active cancers on treatment…).

Patients treated with proton-pump inhibitors or other concomitant medication with potential for interactions reducing exposure to atazanavir

Contacts and Locations

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Please refer to this study by its ClinicalTrials.gov identifier: NCT01599364